Systematic discovery of virus-perturbed molecular pathways linking to schizophrenia

Guanmei Liang; Wenjuan Yi; Yanjun Li; Yue Gao; Lang Huang; Yanmei Lin; Chunlin Chen; Xinping Yang

doi:10.59717/j.xinn-med.2024.100062

The Innovation Medicine > 2024 Vol. 2 > No. 2 > 100062

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Systematic discovery of virus-perturbed molecular pathways linking to schizophrenia

1.
Center for Genetics and Developmental Systems Biology, Southern Medical University, Guangzhou 510515, China
2.
Department of Obstetrics & Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
3.
State Key Laboratory of Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
4.
Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
5.
Central Laboratory, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523058, China
6.
Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou 510515, China
7.
Guangdong Key Laboratory of Psychiatric Disorders, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

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Corresponding authors: xpyang1@smu.edu.cn (X.Y.); ccl1@smu.edu.cn (C.C.)
Received Date: July 18, 2023

Accepted Date: February 03, 2024

Published Online: April 08, 2024

The Innovation Medicine 2(2), https://doi.org/10.59717/j.xinn-med.2024.100062 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Viral proteins tend to interact with host proteins encoded by disease candidate genes of psychiatric disorders.
  
  Both immune and non-immune genes associated with schizophrenia are likely to be targets of the viral proteins.
  
  Ninety-six proteins interacting with HIV-1 Vpr are identified using pull-downs coupled with mass spectrometry.
  
  HIV-1 Vpr impairs object recognition and enhanced anxiety behaviors.

ABSTRACT

ABSTRACT

Virus infections increase risk of psychiatric disorders. Immune activation-mediated perturbation of cellular function is currently proposed as a potential mechanism. Here, we report an alternative mechanism: viral protein-mediated perturbation of molecular pathways. We collected high-quality interactions between human proteins and proteins of neurotrophic viruses, and found that viral targets were enriched with candidate genes of psychiatric disorders, such as schizophrenia (SCZ) and autism spectrum disorder. The viral targets were further mapped onto a high-quality protein interaction network for SCZ (the SCZ Network), and the viral proteins tend to bind hub proteins in the network, suggesting that viral proteins may perturb molecular pathways involved in SCZ. Both immune genes and non-immune genes in this network are likely to be targets of viral proteins, suggesting that the viral infection may lead to SCZ via perturbing immune and nonimmune functions. Using pull-downs coupled with mass spectrometry, 96 human proteins were identified to interact with HIV-1 Vpr. These HIV-1 Vpr targets are enriched with proteins encoded by SCZ candidate genes. AAVs carrying HIV-1 Vpr were stereotactically injected into the prefrontal cortex of mice, and the mice with HIV-1 Vpr expression displayed impairments in object recognition and enhanced anxiety. These results suggest that viruses infecting the brain cells may interfere with cellular functions of the brain through interactions between viral proteins and host proteins.

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REFERENCES

[1]	Dyer, M.D., Murali, T.M., and Sobral, B.W. (2008). The landscape of human proteins interacting with viruses and other pathogens. PLoS Pathog. 4: e32. DOI: 10.1371/journal.ppat.0040032. View in Article CrossRef Google Scholar Scopus
[2]	Itzhaki, Z. (2011). Domain-domain interactions underlying herpesvirus-human protein-protein interaction networks. PLoS One 6: e21724. DOI: 10.1371/journal.pone.0021724. View in Article CrossRef Google Scholar Scopus
[3]	Dunker, A.K., Cortese, M.S., Romero, P., et al. (2005). Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J. 272: 5129−5148. DOI: 10.1111/j.1742-4658.2005.04948.x. View in Article CrossRef Google Scholar Scopus
[4]	Oldfield, C.J., Meng, J., Yang, J.Y., et al. (2008). Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners. BMC Genomics. 9 Suppl 1 :S1. DOI: 10.1186/1471-2164-9-S1-S1. View in Article Google Scholar
[5]	Koponen, H., Rantakallio, P., Veijola, J., et al. (2004). Childhood central nervous system infections and risk for schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 254: 9−13. DOI: 10.1007/s00406-004-0485-2. View in Article CrossRef Google Scholar Scopus
[6]	Al-Beltagi, M., Saeed, N.K., Elbeltagi, R., et al. (2023). Viruses and autism: A bi-mutual cause and effect. World J. Virol. 12: 172−192. DOI: 10.5501/wjv.v12.i3.172. View in Article CrossRef Google Scholar
[7]	Karimi, Z., Chenari, M., Rezaie, F., et al. (2022). Proposed pathway linking respiratory infections with depression. Clin. Psychopharmacol. Neurosci. 20: 199−210. DOI: 10.9758/cpn.2022.20.2.199. View in Article CrossRef Google Scholar
[8]	Kahn, R.S., Sommer, I.E., Murray, R.M., et al. (2015). Schizophrenia. Nat. Rev. Dis. Primers 1: 15067. DOI: 10.1038/nrdp.2015.67. View in Article CrossRef Google Scholar Scopus
[9]	Riley, B. (2004). Linkage studies of schizophrenia. Neurotox. Res. 6: 17−34. DOI: 10.1007/BF03033293. View in Article CrossRef Google Scholar Scopus
[10]	Neves-Pereira, M., Cheung, J.K., Pasdar, A., et al. (2005). BDNF gene is a risk factor for schizophrenia in a Scottish population. Mol. Psychiatry 10: 208−212. DOI: 10.1038/sj.mp.4001575. View in Article CrossRef Google Scholar Scopus
[11]	Xu, B., Wratten, N., Charych, E.I., et al. (2005). Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder. PLoS Med. 2: e263. DOI: 10.1371/journal.pmed.0020263. View in Article CrossRef Google Scholar Scopus
[12]	Chen, C.H., Lee, Y.R., Chung, M.Y., et al. (1999). Systematic mutation analysis of the catechol O-methyltransferase gene as a candidate gene for schizophrenia. Am. J. Psychiatry 156: 1273−1275. DOI: 10.1176/ajp.156.8.1273. View in Article CrossRef Google Scholar Scopus
[13]	Hodgkinson, C.A., Goldman, D., Jaeger, J., et al. (2004). Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am. J. Hum. Genet. 75: 862−872. DOI: 10.1086/425586. View in Article CrossRef Google Scholar
[14]	Cheah, S.Y., Lawford, B.R., Young, R.M., et al. (2015). Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia. Eur. Psychiatry 30: 486−491. DOI: 10.1016/j.eurpsy.2015.01.008. View in Article CrossRef Google Scholar Scopus
[15]	Hahn, C.G., Wang, H.Y., Cho, D.S., et al. (2006). Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med. 12: 824−828. DOI: 10.1038/nm1418. View in Article CrossRef Google Scholar Scopus
[16]	Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., et al. (2002). Neuregulin 1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71: 877−892. DOI: 10.1086/342734. View in Article CrossRef Google Scholar
[17]	Pae, C.U., Yu, H.S., Amann, D., et al. (2008). Association of the trace amine associated receptor 6 (TAAR6) gene with schizophrenia and bipolar disorder in a Korean case control sample. J. Psychiatr. Res. 42: 35−40. DOI: 10.1016/j.jpsychires.2006.09.011. View in Article CrossRef Google Scholar Scopus
[18]	Mukai, J., Liu, H., Burt, R.A., et al. (2004). Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat. Genet. 36: 725−731. DOI: 10.1038/ng1375. View in Article CrossRef Google Scholar Scopus
[19]	Chow, T.J., Tee, S.F., Loh, S.Y., et al. (2018). Variants in ZNF804A and DTNBP1 assessed for cognitive impairment in schizophrenia using a multiplex family-based approach. Psychiatry Res. 270: 1166−1167. DOI: 10.1016/j.psychres.2018.04.051. View in Article CrossRef Google Scholar Scopus
[20]	Chen, J., Calhoun, V.D., Lin, D., et al. (2019). Shared genetic risk of schizophrenia and gray matter reduction in 6p22.1. Schizophr. Bull. 45 :222-232. DOI: 10.1093/schbul/sby010. View in Article Google Scholar
[21]	Autism Spectrum Disorders Working Group of The Psychiatric Genomics, C. (2017). Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. Mol. Autism 8 :21. DOI: 10.1186/s13229-017-0137-9. View in Article Google Scholar
[22]	McCarthy, S.E., Makarov, V., Kirov, G., et al. (2009). Microduplications of 16p11.2 are associated with schizophrenia. Nat. Genet. 41 :1223-1227. DOI: 10.1038/ng.474. View in Article Google Scholar
[23]	Cleynen, I., Engchuan, W., Hestand, M.S., et al. (2020). Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion. Mol. Psychiatry DOI: 10.1038/s41380-020-0654-3. View in Article Google Scholar
[24]	Gao, Y., Li, Y., Li, S., et al. (2021). Systematic discovery of signaling pathways linking immune activation to schizophrenia. iScience 24: 103209. DOI: 10.1016/j.isci.2021.103209. View in Article CrossRef Google Scholar Scopus
[25]	Camargo, L.M., Collura, V., Rain, J.C., et al. (2007). Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol. Psychiatry 12: 74−86. DOI: 10.1038/sj.mp.4001880. View in Article CrossRef Google Scholar Scopus
[26]	Facal, F., and Costas, J. (2019). Evidence of association of the DISC1 interactome gene set with schizophrenia from GWAS. Prog Neuropsychopharmacol Biol. Psychiatry 95: 109729. DOI: 10.1016/j.pnpbp.2019.109729. View in Article CrossRef Google Scholar Scopus
[27]	Schwarz, E., Izmailov, R., Lio, P., et al. (2016). Protein interaction networks link schizophrenia risk loci to synaptic function. Schizophr. Bull. 42: 1334−1342. DOI: 10.1093/schbul/sbw035. View in Article CrossRef Google Scholar
[28]	Nielsen, S.M., Toftdahl, N.G., Nordentoft, M., et al. (2017). Association between alcohol, cannabis, and other illicit substance abuse and risk of developing schizophrenia: A nationwide population based register study. Psychol Med. 47: 1668−1677. DOI: 10.1017/S0033291717000162. View in Article CrossRef Google Scholar Scopus
[29]	Schmidt-Kastner, R., van Os, J., Esquivel, G., et al. (2012). An environmental analysis of genes associated with schizophrenia: Hypoxia and vascular factors as interacting elements in the neurodevelopmental model. Mol. Psychiatry 17: 1194−1205. DOI: 10.1038/mp.2011.183. View in Article CrossRef Google Scholar Scopus
[30]	Jones, P., and Cannon, M. (1998). The new epidemiology of schizophrenia. Psychiatr. Clin. North Am. 21: 1−25. DOI: 10.1016/s0193-953x(05)70358-0. View in Article CrossRef Google Scholar Scopus
[31]	Dickerson, F.B., Boronow, J.J., Stallings, C., et al. (2003). Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia. Arch. Gen. Psychiatry 60: 466−472. DOI: 10.1001/archpsyc.60.5.466. View in Article CrossRef Google Scholar Scopus
[32]	Cannon, M., Cotter, D., Coffey, V.P., et al. (1996). Prenatal exposure to the 1957 influenza epidemic and adult schizophrenia: a follow-up study. Br. J. Psychiatry 168: 368−371. DOI: 10.1192/bjp.168.3.368. View in Article CrossRef Google Scholar
[33]	Brown, A.S., Schaefer, C.A., Wyatt, R.J., et al. (2000). Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: A prospective birth cohort study. Schizophr. Bull. 26: 287−295. DOI: 10.1093/oxfordjournals.schbul.a033453. View in Article CrossRef Google Scholar Scopus
[34]	Estes, M.L., and McAllister, A.K. (2016). Maternal immune activation: Implications for neuropsychiatric disorders. Science 353: 772−777. DOI: 10.1126/science.aag3194. View in Article CrossRef Google Scholar Scopus
[35]	Closson, K., McLinden, T., Patterson, T.L., et al. (2019). HIV, schizophrenia, and all-cause mortality: a population-based cohort study of individuals accessing universal medical care from 1998 to 2012 in British Columbia, Canada. Schizophr. Res. 209: 198−205. DOI: 10.1016/j.schres.2019.04.020. View in Article CrossRef Google Scholar
[36]	Rantakallio, P., Jones, P., Moring, J., et al. (1997). Association between central nervous system infections during childhood and adult onset schizophrenia and other psychoses: A 28-year follow-up. Int. J. Epidemiol. 26: 837−843. DOI: 10.1093/ije/26.4.837. View in Article CrossRef Google Scholar Scopus
[37]	Khandaker, G.M., Zimbron, J., Dalman, C., et al. (2012). Childhood infection and adult schizophrenia: a meta-analysis of population-based studies. Schizophr. Res. 139: 161−168. DOI: 10.1016/j.schres.2012.05.023. View in Article CrossRef Google Scholar
[38]	Dalman, C., Allebeck, P., Gunnell, D., et al. (2008). Infections in the CNS during childhood and the risk of subsequent psychotic illness: A cohort study of more than one million Swedish subjects. Am. J. Psychiatry 165: 59−65. DOI: 10.1176/appi.ajp.2007.07050740. View in Article CrossRef Google Scholar Scopus
[39]	Liang, W., and Chikritzhs, T. (2012). Early childhood infections and risk of schizophrenia. Psychiatry Res. 200: 214−217. DOI: 10.1016/j.psychres.2012.06.007. View in Article CrossRef Google Scholar Scopus
[40]	Geprags, A., Burgin, D., Fegert, J.M., et al. (2022). The Impact of mental health and sociodemographic characteristics on quality of life and life satisfaction during the second year of the COVID-19 pandemic-results of a population-based survey in Germany. Int. J. Environ. Res. Public Health 19 . DOI: 10.3390/ijerph19148734. View in Article Google Scholar
[41]	Sigurethardottir, S., Aspelund, T., Guethmundsdottir, D.G., et al. (2023). Mental health and sociodemographic characteristics among Icelanders, data from a cross-sectional study in Iceland. BMC Psychiatry 23: 30. DOI: 10.1186/s12888-022-04504-y. View in Article CrossRef Google Scholar Scopus
[42]	Shears, P. (2007). Poverty and infection in the developing world: Healthcare-related infections and infection control in the tropics. J. Hosp. Infect. 67: 217−224. DOI: 10.1016/j.jhin.2007.08.016. View in Article CrossRef Google Scholar Scopus
[43]	Hubbard, G., den Daas, C., Johnston, M., et al. (2021). Sociodemographic and psychological risk factors for anxiety and depression: Findings from the COVID-19 health and adherence research in Scotland on mental health (CHARIS-MH) cross-sectional survey. Int. J. Behav. Med. 28: 788−800. DOI: 10.1007/s12529-021-09967-z. View in Article CrossRef Google Scholar
[44]	Mohan, M., Perry, B.I., Saravanan, P., et al. (2021). COVID-19 in people with schizophrenia: potential mechanisms linking schizophrenia to poor prognosis. Front. Psychiatry 12: 666067. DOI: 10.3389/fpsyt.2021.666067. View in Article CrossRef Google Scholar
[45]	Buka, S.L., Cannon, T.D., Torrey, E.F., et al. (2008). Maternal exposure to herpes simplex virus and risk of psychosis among adult offspring. Biol. Psychiatry 63: 809−815. DOI: 10.1016/j.biopsych.2007.09.022. View in Article CrossRef Google Scholar
[46]	Brown, A.S., and Derkits, E.J. (2010). Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. Am. J. Psychiatry 167: 261−280. DOI: 10.1176/appi.ajp.2009.09030361. View in Article CrossRef Google Scholar Scopus
[47]	Boulanger, L.M. (2009). Immune proteins in brain development and synaptic plasticity. Neuron 64: 93−109. DOI: 10.1016/j.neuron.2009.09.001. View in Article CrossRef Google Scholar
[48]	Morimoto, K., and Nakajima, K. (2019). Role of the immune system in the development of the central nervous system. Front. Neurosci. 13: 916. DOI: 10.3389/fnins.2019.00916. View in Article CrossRef Google Scholar
[49]	Taylor, J.P., Pomerantz, R., Bagasra, O., et al. (1992). TAR-independent transactivation by Tat in cells derived from the CNS: A novel mechanism of HIV-1 gene regulation. EMBO J. 11: 3395−3403. DOI: 10.1002/j.1460-2075.1992.tb05418.x. View in Article CrossRef Google Scholar Scopus
[50]	Jager, S., Cimermancic, P., Gulbahce, N., et al. (2011). Global landscape of HIV-human protein complexes. Nature 481: 365−370. DOI: 10.1038/nature10719. View in Article CrossRef Google Scholar Scopus
[51]	Safa, A., Badrlou, E., Arsang-Jang, S., et al. (2020). Expression of NF-kappaB associated lncRNAs in schizophrenia. Sci. Rep. 10: 18105. DOI: 10.1038/s41598-020-75333-w. View in Article CrossRef Google Scholar
[52]	Murphy, C.E., Lawther, A.J., Webster, M.J., et al. (2020). Nuclear factor kappa B activation appears weaker in schizophrenia patients with high brain cytokines than in non-schizophrenic controls with high brain cytokines. J. Neuroinflammation 17: 215. DOI: 10.1186/s12974-020-01890-6. View in Article CrossRef Google Scholar Scopus
[53]	Okubo, Y., Suhara, T., Suzuki, K., et al. (1997). Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 385: 634−636. DOI: 10.1038/385634a0. View in Article CrossRef Google Scholar Scopus
[54]	Koike, S., Takizawa, R., Nishimura, Y., et al. (2013). Reduced but broader prefrontal activity in patients with schizophrenia during n-back working memory tasks: a multi-channel near-infrared spectroscopy study. J. Psychiatr. Res. 47: 1240−1246. DOI: 10.1016/j.jpsychires.2013.05.009. View in Article CrossRef Google Scholar
[55]	Tortorella, D., Gewurz, B.E., Furman, M.H., et al. (2000). Viral subversion of the immune system. Annu. Rev. Immunol. 18: 861−926. DOI: 10.1146/annurev.immunol.18.1.861. View in Article CrossRef Google Scholar Scopus
[56]	Alcami, A., Ghazal, P., and Yewdell, J.W. (2002). Viruses in control of the immune system. Workshop on molecular mechanisms of immune modulation: lessons from viruses. EMBO Rep. 3: 927−932. DOI: 10.1093/embo-reports/kvf200. View in Article CrossRef Google Scholar Scopus
[57]	Obi-Nagata, K., Temma, Y., and Hayashi-Takagi, A. (2019). Synaptic functions and their disruption in schizophrenia: From clinical evidence to synaptic optogenetics in an animal model. Proc. Jpn. Acad. Ser. B. Phys. Biol. Sci. 95: 179−197. DOI: 10.2183/pjab.95.014. View in Article CrossRef Google Scholar Scopus
[58]	Osimo, E.F., Beck, K., Reis Marques, T., et al. (2019). Synaptic loss in schizophrenia: A meta-analysis and systematic review of synaptic protein and mRNA measures. Mol. Psychiatry 24: 549−561. DOI: 10.1038/s41380-018-0041-5. View in Article CrossRef Google Scholar
[59]	Barlati, S., Nibbio, G., and Vita, A. (2021). Schizophrenia during the COVID-19 pandemic. Curr. Opin. Psychiatry 34: 203−210. DOI: 10.1097/YCO.0000000000000702. View in Article CrossRef Google Scholar Scopus
[60]	Hassan, L., Peek, N., Lovell, K., et al. (2021). Disparities in COVID-19 infection, hospitalisation and death in people with schizophrenia, bipolar disorder, and major depressive disorder: A cohort study of the UK Biobank. Mol. Psychiatry 27: 1248−1255. DOI: 10.1038/s41380-021-01344-2. View in Article CrossRef Google Scholar
[61]	Nemani, K., Li, C., Olfson, M., et al. (2021). Association of psychiatric disorders with mortality among patients with COVID-19. JAMA Psychiatry 78: 380−386. DOI: 10.1001/jamapsychiatry.2020.4442. View in Article CrossRef Google Scholar
[62]	Thepmankorn, P., Bach, J., Lasfar, A., et al. (2021). Cytokine storm induced by SARS-CoV-2 infection: the spectrum of its neurological manifestations. Cytokine 138: 155404. DOI: 10.1016/j.cyto.2020.155404. View in Article CrossRef Google Scholar
[63]	Dickerson, F., Jones-Brando, L., Ford, G., et al. (2019). Schizophrenia is associated with an aberrant immune response to epstein-barr virus. Schizophr. Bull. 45: 1112−1119. DOI: 10.1093/schbul/sby164. View in Article CrossRef Google Scholar Scopus
[64]	Fei, E., Ma, X., Zhu, C., et al. (2010). Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-related protein, regulates synapsin I expression. J. Biol. Chem. 285: 38630−38640. DOI: 10.1074/jbc.M110.107912. View in Article CrossRef Google Scholar Scopus
[65]	Xu, J., Sun, J., Chen, J., et al. (2012). RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia. BMC Genomics 13 Suppl 8 :S2. DOI: 10.1186/1471-2164-13-S8-S2. View in Article Google Scholar
[66]	Zhu, L., Wu, X., Xu, B., et al. (2021). The machine learning algorithm for the diagnosis of schizophrenia on the basis of gene expression in peripheral blood. Neurosci. Lett. 745: 135596. DOI: 10.1016/j.neulet.2020.135596. View in Article CrossRef Google Scholar Scopus
[67]	Brucato, N., Guadalupe, T., Franke, B., et al. (2015). A schizophrenia-associated HLA locus affects thalamus volume and asymmetry. Brain Behav. Immun. 46: 311−318. DOI: 10.1016/j.bbi.2015.02.021. View in Article CrossRef Google Scholar Scopus
[68]	Seshasubramanian, V., Raghavan, V., SathishKannan, A.D., et al. (2020). Association of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at amino acid level in individuals with schizophrenia: A study from South India. Int. J. Immunogenet. 47: 501−511. DOI: 10.1111/iji.12507. View in Article CrossRef Google Scholar Scopus
[69]	Chao, Y.L., Shen, Y.C., Liao, D.L., et al. (2008). Association study of HLA-A gene and schizophrenia in Han Chinese from Taiwan. Prog. Neuropsychopharmacol. Biol. Psychiatry 32: 1834−1837. DOI: 10.1016/j.pnpbp.2008.08.009. View in Article CrossRef Google Scholar Scopus
[70]	Liu, Y., Qu, H.Q., Chang, X., et al. (2022). Expansion of schizophrenia gene network knowledge using machine learning selected signals from dorsolateral prefrontal cortex and amygdala RNA-seq data. Front. Psychiatry 13: 797329. DOI: 10.3389/fpsyt.2022.797329. View in Article CrossRef Google Scholar
[71]	Ben-Shachar, D., and Karry, R. (2007). Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. PLoS One 2: e817. DOI: 10.1371/journal.pone.0000817. View in Article CrossRef Google Scholar Scopus
[72]	Jouan, L., Girard, S.L., Dobrzeniecka, S., et al. (2013). Investigation of rare variants in LRP1, KPNA1, ALS2CL and ZNF480 genes in schizophrenia patients reflects genetic heterogeneity of the disease. Behav. Brain Funct. 9: 9. DOI: 10.1186/1744-9081-9-9. View in Article CrossRef Google Scholar Scopus
[73]	Kowalczyk, M., Kucia, K., Owczarek, A., et al. (2018). Association studies of HSPA1A and HSPA1L gene polymorphisms with schizophrenia. Arch. Med. Res. 49: 342−349. DOI: 10.1016/j.arcmed.2018.10.002. View in Article CrossRef Google Scholar
[74]	Segev, S., Yitzhaky, A., Ben Shachar, D., et al. (2023). VDAC genes down-regulation in brain samples of individuals with schizophrenia is revealed by a systematic meta-analysis. Neurosci. Res. 192: 83−92. DOI: 10.1016/j.neures.2023.01.012. View in Article CrossRef Google Scholar Scopus
[75]	Kim, T., Park, J.K., Kim, H.J., et al. (2010). Association of histone deacetylase genes with schizophrenia in Korean population. Psychiatry Res. 178: 266−269. DOI: 10.1016/j.psychres.2009.05.007. View in Article CrossRef Google Scholar Scopus
[76]	Kebir, O., Chaumette, B., Fatjo-Vilas, M., et al. (2014). Family-based association study of common variants, rare mutation study and epistatic interaction detection in HDAC genes in schizophrenia. Schizophr. Res. 160: 97−103. DOI: 10.1016/j.schres.2014.09.029. View in Article CrossRef Google Scholar Scopus
[77]	Han, C., Cui, K., Bi, X., et al. (2019). Association between polymorphism of the NEDD4 gene and cognitive dysfunction of schizophrenia patients in Chinese Han population. BMC Psychiatry 19: 405. DOI: 10.1186/s12888-019-2386-y. View in Article CrossRef Google Scholar Scopus
[78]	Maudet, C., Sourisce, A., Dragin, L., et al. (2013). HIV-1 Vpr induces the degradation of ZIP and sZIP, adaptors of the NuRD chromatin remodeling complex, by hijacking DCAF1/VprBP. PLoS One 8: e77320. DOI: 10.1371/journal.pone.0077320. View in Article CrossRef Google Scholar
[79]	Richetto, J., and Meyer, U. (2021). Epigenetic modifications in schizophrenia and related disorders: molecular scars of senvironmental exposures and source of phenotypic variability. Biol. Psychiatry 89: 215−226. DOI: 10.1016/j.biopsych.2020.03.008. View in Article CrossRef Google Scholar
[80]	Sellgren, C.M., Gracias, J., Watmuff, B., et al. (2019). Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. Nat. Neurosci. 22: 374−385. DOI: 10.1038/s41593-018-0334-7. View in Article CrossRef Google Scholar Scopus
[81]	Guang, S., Pang, N., Deng, X., et al. (2018). Synaptopathology involved in autism spectrum disorder. Front. Cell Neurosci. 12: 470. DOI: 10.3389/fncel.2018.00470. View in Article CrossRef Google Scholar Scopus
[82]	Sacai, H., Sakoori, K., Konno, K., et al. (2020). Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex. Nat. Commun. 11: 5140. DOI: 10.1038/s41467-020-18861-3. View in Article CrossRef Google Scholar Scopus
[83]	Haddad, F.L., Patel, S.V., and Schmid, S. (2020). Maternal immune activation by poly I:C as a preclinical model for neurodevelopmental disorders: A focus on autism and schizophrenia. Neurosci. Biobehav. Rev. 113: 546−567. DOI: 10.1016/j.neubiorev.2020.04.012. View in Article CrossRef Google Scholar
[84]	Massrali, A., Adhya, D., Srivastava, D.P., et al. (2022). Virus-induced maternal immune activation as an environmental factor in the etiology of autism and schizophrenia. Front. Neurosci. 16: 834058. DOI: 10.3389/fnins.2022.834058. View in Article CrossRef Google Scholar
[85]	Capellan, R., Orihuel, J., Marcos, A., et al. (2023). Interaction between maternal immune activation and peripubertal stress in rats: Impact on cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome. Transl. Psychiatry 13: 84. DOI: 10.1038/s41398-023-02378-6. View in Article CrossRef Google Scholar
[86]	Zhao, F., Li, B., Yang, W., et al. (2022). Brain-immune interaction mechanisms: Implications for cognitive dysfunction in psychiatric disorders. Cell Prolif. 55: e13295. DOI: 10.1111/cpr.13295. View in Article CrossRef Google Scholar
[87]	Nosik, M., Lavrov, V., and Svitich, O. (2021). HIV infection and related mental disorders. Brain Sci. 11 . DOI: 10.3390/brainsci11020248. View in Article Google Scholar
[88]	Linnaranta, O., Trontti, K.T., Honkanen, J., et al. (2021). Peripheral metabolic state and immune system in first-episode psychosis-a gene expression study with a prospective one-year follow-up. J. Psychiatr. Res. 137: 383−392. DOI: 10.1016/j.jpsychires.2021.03.013. View in Article CrossRef Google Scholar
[89]	Estes, M.L., and McAllister, A.K. (2015). Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat. Rev. Neurosci. 16: 469−486. DOI: 10.1038/nrn3978. View in Article CrossRef Google Scholar Scopus
[90]	Robson, M.J., Quinlan, M.A., and Blakely, R.D. (2017). Immune system activation and depression: roles of serotonin in the central nervous system and periphery. ACS Chem. Neurosci. 8: 932−942. DOI: 10.1021/acschemneuro.6b00412. View in Article CrossRef Google Scholar
[91]	Ruiz, N.A.L., Del Angel, D.S., Brizuela, N.O., et al. (2022). Inflammatory process and immune system in major depressive disorder. Int. J. Neuropsychopharmacol. 25: 46−53. DOI: 10.1093/ijnp/pyab072. View in Article CrossRef Google Scholar
[92]	Fleury, M.J., Grenier, G., Bamvita, J.M., et al. (2011). Typology of adults diagnosed with mental disorders based on socio-demographics and clinical and service use characteristics. BMC Psychiatry 11: 67. DOI: 10.1186/1471-244X-11-67. View in Article CrossRef Google Scholar Scopus
[93]	Kostiuk, N., and Pachet, A. (2021). Schizophrenia vs. encephalitis: A neuropsychological case study. Schizophr. Res. Cogn. 26: 100203. DOI: 10.1016/j.scog.2021.100203. View in Article CrossRef Google Scholar Scopus
[94]	Riedmuller, R., and Muller, S. (2017). Ethical implications of the mild encephalitis hypothesis of schizophrenia. Front. Psychiatry 8: 38. DOI: 10.3389/fpsyt.2017.00038. View in Article CrossRef Google Scholar Scopus
[95]	Abrahao, A.L., Focaccia, R., and Gattaz, W.F. (2005). Childhood meningitis increases the risk for adult schizophrenia. World J. Biol. Psychiatry 6 Suppl 2 :44-48. DOI: 10.1080/15622970510030063. View in Article Google Scholar
[96]	Taquet, M., Sillett, R., Zhu, L., et al. (2022). Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: An analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry 9: 815−827. DOI: 10.1016/S2215-0366(22)00260-7. View in Article CrossRef Google Scholar

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Liang G., Yi W., Li Y., et al., (2024). Systematic discovery of virus-perturbed molecular pathways linking to schizophrenia. The Innovation Medicine 2(2): 100062. https://doi.org/10.59717/j.xinn-med.2024.100062

Liang G., Yi W., Li Y., et al., (2024). Systematic discovery of virus-perturbed molecular pathways linking to schizophrenia. The Innovation Medicine 2(2): 100062. https://doi.org/10.59717/j.xinn-med.2024.100062

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Systematic discovery of virus-perturbed molecular pathways linking to schizophrenia

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